Chemical Methodologies
7.4 (Q1)
CiteScore2024
Q2
Web of Science

Computational Insights into the Anti-Inflammatory Potential of Ocimum americanum Phytochemicals in Malaria-Associated Cytokine Dysregulation

Document Type : Original Article

Authors

Nur Balqis Maulydia 1
Syahputra Wibowo 1
Josephine Elizabeth Siregar 1
Rinaldi Idroes 2
Rony Abdi Syahputra 3
Putri Cahaya Situmorang 4

1 Eijkman Research Center for Molecular Biology, National Research and Innovation Agency, Jalan Raya Bogor KM. 46, Cibinong, Bogor 16911, Indonesia

2 Department of Pharmacy, Faculty Mathematics and Natural Science, Universitas Syiah Kuala, Banda Aceh, Indonesia

3 Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan, Indonesia

4 Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Medan, Indonesia

https://doi.org/10.48309/chemm.2026.570365.2078
Abstract
Ocimum americanum is a traditionally used medicinal plant that remains pharmacologically underexplored in the context of malaria-associated inflammation. In this study, an integrated chemical and computational approach was employed to investigate the potential molecular mechanisms underlying the anti-inflammatory relevance of Ocimum americanum –derived phytochemicals. A curated set of literature-reported secondary metabolites representative of Ocimum americanum  was analyzed using network pharmacology to explore their interactions with malaria-, inflammation-, and oxidative stress–related targets. Network analysis identified a set of core regulatory targets shared across disease contexts, with functional enrichment highlighting pathways associated with cytokine-mediated signaling and redox homeostasis. Pro-inflammatory mediators, particularly interleukin-6 (IL-6) and tumor necrosis factor (TNF), emerged as central hub nodes within the protein–protein interaction network, suggesting their relevance as key molecular convergence points. To further assess mechanistic plausibility, molecular docking and molecular dynamics simulation were performed against selected hub targets. Among the evaluated phytochemicals, ursolic acid demonstrated the most favorable binding affinities toward TNF and IL-6, indicating a strong theoretical potential for modulating cytokine-driven inflammatory signaling. Collectively, these findings provide computational evidence supporting the multi-target anti-inflammatory potential of Ocimum americanum  phytochemicals in malaria-associated hyperinflammation. This study positions ursolic acid as a promising lead compound and establishes a mechanistically informed in silico framework to guide future experimental validation and therapeutic exploration.

Graphical Abstract

Computational Insights into the Anti-Inflammatory Potential of Ocimum americanum Phytochemicals in Malaria-Associated Cytokine Dysregulation

Keywords

American basil
Ursolic acid
Malaria-associated inflammation
Network pharmacology

Subjects

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[1]     Organization, W.H. WHO malaria policy advisory group (MPAG) meeting report, 18–20 April 2023. World Health Organization, 2023.
[2]     World Health Organization, “World malaria report 2024: addressing inequity in the global malaria response,” Geneva, 2024.
[3]     Kementerian Kesehatan Republik Indonesia, “Kemenkes Luncurkan Peta Jalan Eliminasi Malaria dan Pencegahan Penularan Kembali di Indonesia,” Sehat Negeriku – Kementerian Kesehatan RI. Accessed: Jun. 26, 2025.
[4]     Gomes, A.R.Q., Cunha, N., Varela, E.L.P., Brígido, H.P.C., Vale, V.V., Dolabela, M.F., Percário, S. Oxidative stress in malaria: potential benefits of antioxidant therapy. International Journal of Molecular Sciences, 2022, 23(11), 5949.
[5]     Vasquez, M., Zuniga, M., Rodriguez, A. Oxidative stress and pathogenesis in malaria. Frontiers in Cellular and Infection Microbiology, 2021, 11, 768182.
[6]     Kotepui, K.U., Mahittikorn, A., Mala, W., Lasom, S., Masangkay, F.R., Majima, H.J., Kotepui, M. Total antioxidant status levels in malaria: a systematic review and meta-analysis. Malaria Journal, 2024, 23(1), 198.
[7]     Popa, G.L., Popa, M.I. Recent advances in understanding the inflammatory response in malaria: a review of the dual role of cytokines. Journal of Immunology Research, 2021, 2021(1), 7785180.
[8]     Wilairatana, P., Mala, W., Milanez, G.D.J., Masangkay, F.R., Kotepui, K.U., Kotepui, M. Increased interleukin-6 levels associated with malaria infection and disease severity: a systematic review and meta-analysis. Scientific Reports, 2022, 12(1), 5982.
[9]     Obeagu, E.I. Role of cytokines in immunomodulation during malaria clearance. Annals of Medicine and Surgery, 2024, 86(5), 2873-2882.
[10] Borges, T.K., Alves, E.A., Vasconcelos, H.A., Carneiro, F.P., Nicola, A.M., Magalhães, K.G., Muniz-Junqueira, M.I. Differences in the modulation of reactive species, lipid bodies, cyclooxygenase-2, 5-lipoxygenase and PPAR-γ in cerebral malaria-susceptible and resistant mice. Immunobiology, 2017, 222(4), 604-619.
[11] Zahran, E.M., Abdelmohsen, U.R., Khalil, H.E., Desoukey, S.Y., Fouad, M.A., Kamel, M.S. Diversity, phytochemical and medicinal potential of the genus Ocimum L. (Lamiaceae). Phytochemistry Reviews, 2020, 19(4), 907-953.
[12] Zengin, G., Ferrante, C., Gnapi, D.E., Sinan, K.I., Orlando, G., Recinella, L., Chiavaroli, A. Comprehensive approaches on the chemical constituents and pharmacological properties of flowers and leaves of American basil (Ocimum americanum L). Food Research International, 2019, 125, 108610.
[13] Maddi, R., Amani, P., Bhavitha, S., Gayathri, T., Lohitha, T. A review on Ocimum species: Ocimum americanum L., Ocimum basilicum L., Ocimum gratissimum L. and Ocimum tenuiflorum L. International Journal of Research in Ayurveda and Pharmacy, 2019, 10, 41-48.
[14] Merawi, E., Belay, T.B. Distribution, local use, and bio-prospecting opportunity of Ocimum americanum L. in Northwestern part of the Amhara Region, Ethiopia. Sustinere: Journal of Environment and Sustainability, 2024, 8(1), 123-137.
[15] Ali, H., Nguta, J., Musila, F., Ole-Mapenay, I., Matara, D., Mailu, J. Evaluation of antimicrobial activity, cytotoxicity, and phytochemical composition of Ocimum americanum L. (Lamiaceae). Evidence‐Based Complementary and Alternative Medicine, 2022, 2022(1), 6484578.
[16] Mohamed Abdoul-Latif, F., Elmi, A., Merito, A., Nour, M., Risler, A., Ainane, A., Ainane, T. Essential oils of Ocimum basilicum L. and Ocimum americanum L. from Djibouti: Chemical composition, antimicrobial and cytotoxicity evaluations. Processes, 2022, 10(9), 1785.
[17] Vivek-Ananth, R., Mohanraj, K., Sahoo, A.K., Samal, A. IMPPAT 2.0: an enhanced and expanded phytochemical atlas of Indian medicinal plants. ACS Omega, 2023, 8(9), 8827-8845.
[18] Luanda, A., Ripanda, A., Sahini, M.G., Makangara, J.J. Ethnomedicinal uses, phytochemistry and pharmacological study of Ocimum americanum L.: A review. Phytomedicine Plus, 2023, 3(2), 100433.
[19] Wirtu, S.F., Mishra, A.K., Jule, L.T., Ramaswamy, K. Ocimum basilicum and Ocimum americanum: A Systematic Literature Review on Chemical Compositions and Antimicrobial Properties. Natural Product Communications, 2024, 19(4), 1934578X241247640.
[20] Zengin, G., Ferrante, C., Gnapi, D.E., Sinan, K.I., Orlando, G., Recinella, L., Chiavaroli, A. Comprehensive approaches on the chemical constituents and pharmacological properties of flowers and leaves of American basil (Ocimum americanum L). Food Research International, 2019, 125, 108610.
[21] Vieira, R.F., Grayer, R.J., Paton, A.J. Chemical profiling of Ocimum americanum using external flavonoids. Phytochemistry, 2003, 63(5), 555-567.
[22] Khairan, K., Maulydia, N.B., Faddillah, V., Tallei, T.E., Fauzi, F.M., Idroes, R. Uncovering anti-inflammatory potential of Lantana camara Linn: Network pharmacology and in vitro studies. Narra J, 2024, 4(2), e894.
[23] Daina, A., Michielin, O., Zoete, V. SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic acids research, 2019, 47(W1), W357-W364.
[24] Hamosh, A., Scott, A.F., Amberger, J.S., Bocchini, C.A., McKusick, V.A. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Research, 2005, 33(suppl_1), D514-D517.
[25] Sailah, I., Tallei, T.E., Safitri, L., Tamala, Y., Halimatushadyah, E., Ekatanti, D., Celik, I. A network pharmacology approach to elucidate the anti-inflammatory and antioxidant effects of bitter leaf (Vernonia amygdalina Del.). Narra J, 2024, 4(3), e1016.
[26] Szklarczyk, D., Kirsch, R., Koutrouli, M., Nastou, K., Mehryary, F., Hachilif, R., Pyysalo, S. The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Research, 2023, 51(D1), D638-D646.
[27] Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Ramage, D., Ideker, T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Research, 2003, 13(11), 2498-2504.
[28] Situmorang, P.C., Wibowo, S., Ilyas, S., Nugraha, S.E., Nugraha, A.P., Utami, D.T., Abd Rahman, N.M.A.N., Mukra, R. Therapeutic potential of Gynura procumbens in enhancing cytokine regulation in the cervix of rats induced by 7, 12-dimethylbenz (a) anthracene: In vivo and in silico investigations. Journal of Functional Foods, 2025, 132, 106963.
[29] Situmorang, P.C., Wibowo, S., Ilyas, S., Sari, R.M., Nugraha, A.P., Ibrahim, A., Fitrianita, A., Abiyyu, N., Syahputra, R.A. Rhodomyrtus tomentosa attenuates HER2 expression and modulates apoptotic pathways in DMBA-induced breast carcinogenesis: In vivo and in silico insights. Journal of Agriculture and Food Research, 2025, 102360.
[30] Maulydia, N.B., Khairan, K., Tallei, T.E., Idroes, R. Metabolomic profiling and anti-inflammatory activity of Blumea balsamifera: Insights from in silico and in vitro studies. Pharmacia, 2025, 72, 1-15.
[31] Wróblewski, K., Zalewski, M., Kuriata, A., Kmiecik, S. CABS-flex 3.0: an online tool for simulating protein structural flexibility and peptide modeling. Nucleic Acids Research, 2025, gkaf412.
[32] Mahendran, G., Vimolmangkang, S. Chemical compositions, antioxidant, antimicrobial, and mosquito larvicidal activity of Ocimum americanum L. and Ocimum basilicum L. leaf essential oils. BMC Complementary Medicine and Therapies, 2023, 23(1), 390.
[33] Muthengi, A., Karithi, A., Ngugi, F., Mworia, J.K. Phytochemical screening and repellence potencies of bioactive molecules of plant extracts derived from Ocimum suave, Ocimum americanum and Eucalyptus citriodora against Anopheles gambiae. Malaria Journal, 2025, 24(1), 137.
[34] Chien, P.Y., Lan, Y.H., Wu, I.T., Huang, Y.P., Hung, C.C. Mosloflavone from Fissistigma petelotii ameliorates oncogenic multidrug resistance by STAT3 signaling modulation and P-glycoprotein blockade. Phytomedicine, 2024, 123, 155210.
[35] Allemailem, K.S., Almatroudi, A., Alharbi, H.O.A., AlSuhaymi, N., Alsugoor, M.H., Aldakheel, F.M., Rahmani, A.H. Apigenin: A bioflavonoid with a promising role in disease prevention and treatment. Biomedicines, 2024, 12(6), 1353.
[36] Guan, H., Luo, W., Bao, B., Cao, Y., Cheng, F., Yu, S., Shan, M. A comprehensive review of rosmarinic acid: from phytochemistry to pharmacology and its new insight. Molecules, 2022, 27(10), 3292.
[37] Nguyen, H.N., Ullevig, S.L., Short, J.D., Wang, L., Ahn, Y.J., Asmis, R. Ursolic acid and related analogues: triterpenoids with broad health benefits. Antioxidants, 2021, 10(8), 1161.
[38] Masyita, A., Sari, R.M., Astuti, A.D., Yasir, B., Rumata, N.R., Emran, T.B., Simal-Gandara, J. Terpenes and terpenoids as main bioactive compounds of essential oils, their roles in human health and potential application as natural food preservatives. Food Chemistry: X, 2022, 13, 100217.
[39] Wang, H., Wang, Z., Zhang, Z., Liu, J., Hong, L. β-Sitosterol as a promising anticancer agent for chemoprevention and chemotherapy: mechanisms of action and future prospects. Advances in Nutrition, 2023, 14(5), 1085-1110.
[40] Nisar, M.F., Khadim, M., Rafiq, M., Chen, J., Yang, Y., Wan, C.C. Pharmacological properties and health benefits of eugenol: A comprehensive review. Oxidative Medicine and Cellular Longevity, 2021, 2021(1), 2497354.
[41] Hassanpour, S.H., Doroudi, A. Review of the antioxidant potential of flavonoids as a subgroup of polyphenols and partial substitute for synthetic antioxidants. Avicenna Journal of Phytomedicine, 2023, 13(4), 354.
[42] Grayer, R.J., Kite, G.C., Veitch, N.C., Eckert, M.R., Marin, P.D., Senanayake, P., Paton, A.J. Leaf flavonoid glycosides as chemosystematic characters in Ocimum. Biochemical Systematics and Ecology, 2002, 30(4), 327-342.
[43] Clark, I.A., Cowden, W.B. The pathophysiology of falciparum malaria. Pharmacology & Therapeutics, 2003, 99(2), 221-260.
[44] Hashmi, F., Aqeel, S., Zuberi, U.F., Khan, W. A systematic review and meta-analysis of inflammatory biomarkers associated with malaria infection and disease severity. Cytokine, 2003, 169, 156305.
[45] Kairupan, T.S., Kapantow, N.H., Tallei, T.E., Niode, N.J., Sanggelorang, Y., Rotty, L.W., Wungouw, H.I., Kawengian, S.E., Fatimawali, F., Maulydia, N.B. Mechanistic insights into the anticancer, anti-inflammatory, and antioxidant effects of yellowfin tuna collagen peptides using network pharmacology. Narra J, 2025, 5(1), 1185.
[46] Zhang, J., Luo, Y. Degree centrality, betweenness centrality, and closeness centrality in social network. In 2017 2nd International Conference on Modelling, Simulation and Applied Mathematics, 2017, 300-303.
[47] Hunter, C.A., Jones, S.A. IL-6 as a keystone cytokine in health and disease. Nature Immunology, 2015, 16(5), 448-457.
[48] Chu, W.M. Tumor necrosis factor. Cancer Letters, 2023, 328(2), 222-225.
[49] Libby, P. Inflammatory mechanisms: the molecular basis of inflammation and disease. Nutrition Reviews, 2007, 65(suppl_3), S140-S146.
[50] Dessimoz, C., Škunca, N. The Gene Ontology Handbook. Springer Nature, 2017.
[51] Zhao, M., Wu, F., Tang, Z., Yang, X., Liu, Y., Wang, F., Chen, B. Anti-inflammatory and antioxidant activity of ursolic acid: a systematic review and meta-analysis. Frontiers in Pharmacology, 2023, 14, 1256946.
[52] Zia, K., Ashraf, S., Jabeen, A., Saeed, M., Nur-e-Alam, M., Ahmed, S., Al-Rehaily, A.J., Ul-Haq, Z. Identification of potential TNF-α inhibitors: from in silico to in vitro studies. Scientific Reports, 2020, 10(1), 20974.
[53] Yamada, A.N., Grespan, R., Yamada, Á.T., Silva, E.L., Silva-Filho, S.E., Damião, M.J., de Oliveira Dalalio, M.M., Bersani-Amado, C.A., Cuman, R.K.N. Anti-inflammatory activity of Ocimum americanum L. essential oil in experimental model of zymosan-induced arthritis. The American Journal of Chinese Medicine, 2013, 41(04), 913-926.
[54] Genfi, A.K.A., Larbie, C., Emikpe, B.O., Oyagbemi, A.A., Firempong, C.K., Adjei, C.O. Modulation of oxidative stress and inflammatory cytokines as therapeutic mechanisms of Ocimum americanum L extract in carbon tetrachloride and acetaminophen-induced toxicity in rats. Journal of Evidence-Based Integrative Medicine, 2020, 25, 2515690X20938002.
[55] Sharma, A.D., Kaur, I., Angish, S., Thakur, A., Sania, S., Singh, A. Comparative phytochemistry, antioxidant, antidiabetic, and anti-inflammatory activities of traditionally used Ocimum basilicum L. Ocimum gratissimum L., and Ocimum tenuiflorum L. BioTechnologia, 2022, 103(2), 131.
[56]  Chaiyana, W., Anuchapreeda, S., Punyoyai, C., Neimkhum, W., Lee, K.H., Lin, W.C., Lue, S.C., Viernstein, H., Mueller, M. Ocimum sanctum Linn. as a natural source of skin anti-ageing compounds. Industrial Crops and Products, 2019, 127, 217-224.
 
Chemical Methodologies
Volume 10, Issue 5
May 2026
Pages 566-585

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  • Receive Date 03 December 2025
  • Revise Date 21 January 2026
  • Accept Date 06 February 2026

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